Diallyl disulfide
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Diallyl disulfide (DADS or 4,5-dithia-1,7-octadiene) is an
organosulfur compound Organosulfur compounds are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.g., saccharin. Nature abounds with organosulfur compounds—sulfu ...
derived from
garlic Garlic (''Allium sativum'') is a species of bulbous flowering plant in the genus ''Allium''. Its close relatives include the onion, shallot, leek, chive, Allium fistulosum, Welsh onion and Allium chinense, Chinese onion. It is native to South A ...
and a few other genus ''
Allium ''Allium'' is a genus of monocotyledonous flowering plants that includes hundreds of species, including the cultivated onion, garlic, scallion, shallot, leek, and chives. The generic name ''Allium'' is the Latin word for garlic,Gledhill, Davi ...
'' plants. Along with diallyl trisulfide and diallyl tetrasulfide, it is one of the principal components of the
distilled Distillation, or classical distillation, is the process of separating the components or substances from a liquid mixture by using selective boiling and condensation, usually inside an apparatus known as a still. Dry distillation is the heating ...
oil An oil is any nonpolar chemical substance that is composed primarily of hydrocarbons and is hydrophobic (does not mix with water) & lipophilic (mixes with other oils). Oils are usually flammable and surface active. Most oils are unsaturated ...
of
garlic Garlic (''Allium sativum'') is a species of bulbous flowering plant in the genus ''Allium''. Its close relatives include the onion, shallot, leek, chive, Allium fistulosum, Welsh onion and Allium chinense, Chinese onion. It is native to South A ...
. It is a yellowish liquid which is insoluble in water and has a strong garlic odor. It is produced during the decomposition of
allicin Allicin is an organosulfur compound obtained from garlic, a species in the family Alliaceae. It was first isolated and studied in the laboratory by Chester J. Cavallito and John Hays Bailey in 1944. When fresh garlic is chopped or crushed, the ...
, which is released upon crushing
garlic Garlic (''Allium sativum'') is a species of bulbous flowering plant in the genus ''Allium''. Its close relatives include the onion, shallot, leek, chive, Allium fistulosum, Welsh onion and Allium chinense, Chinese onion. It is native to South A ...
and other plants of the family
Alliaceae Allioideae is a subfamily of monocot flowering plants in the family Amaryllidaceae, order Asparagales. It was formerly treated as a separate family, Alliaceae. The subfamily name is derived from the generic name of the type genus, ''Allium''. ...
. Diallyl disulfide has many of the health benefits of garlic, but it is also an
allergen An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called allergies. In technical terms ...
causing garlic allergy. Highly diluted, it is used as a flavoring in
food Food is any substance consumed by an organism for nutritional support. Food is usually of plant, animal, or fungal origin, and contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals. The substance is inge ...
. It decomposes in the human body into other compounds such as
allyl methyl sulfide Allyl methyl sulfide is an organosulfur compound with the chemical formula CH2=CHCH2SCH3. The molecule features two functional groups, an allyl (CH2=CHCH2) and a sulfide. It is a colourless liquid with a strong odor characteristic of alkyl sulfid ...
.


History

In 1844,
Theodor Wertheim Theodor Wertheim (25 December 1820 – 6 July 1864) was an Austrian chemist born in Vienna. He was the father of gynecologist Ernst Wertheim (1864-1920). He studied organic chemistry in Berlin as a pupil of Eilhard Mitscherlich, and in 1 ...
separated by
steam distillation Steam distillation is a separation process that consists in distilling water together with other volatile and non-volatile components. The steam from the boiling water carries the vapor of the volatiles to a condenser; both are cooled and ret ...
a pungent-smelling substance from garlic and named it "
allyl In organic chemistry, an allyl group is a substituent with the structural formula , where R is the rest of the molecule. It consists of a methylene bridge () attached to a vinyl group (). The name is derived from the scientific name for garlic, ...
sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
." However, only in 1892 could Friedrich Wilhelm Semmler identify diallyl disulfide as one of the components of distilled
garlic oil Garlic oil is the volatile oil derived from garlic. It is usually prepared using steam distillation and can also be produced via distillation using ether. It is used in cooking and as a seasoning, a nutritional supplement, and also as an insecti ...
. The natural precursor of diallyl disulfide,
allicin Allicin is an organosulfur compound obtained from garlic, a species in the family Alliaceae. It was first isolated and studied in the laboratory by Chester J. Cavallito and John Hays Bailey in 1944. When fresh garlic is chopped or crushed, the ...
, was discovered in 1944 by Chester J. Cavallito and John Hays Bailey. In 1947, A. Stoll and E. Seebeck found that
allicin Allicin is an organosulfur compound obtained from garlic, a species in the family Alliaceae. It was first isolated and studied in the laboratory by Chester J. Cavallito and John Hays Bailey in 1944. When fresh garlic is chopped or crushed, the ...
in turn can be produced from the
cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...
derivative
alliin Alliin is a sulfoxide that is a natural constituent of fresh garlic. It is a derivative of the amino acid cysteine. When fresh garlic is chopped or crushed, the enzyme alliinase converts alliin into allicin, which is responsible for the aroma of ...
using the enzyme
alliinase In enzymology, an alliin lyase () is an enzyme that catalyzes the chemical reaction :an ''S''-alkyl-L-cysteine ''S''-oxide \rightleftharpoons an alkyl sulfenate + 2-aminoacrylate Hence, this enzyme has one substrate, ''S''-alkyl-L-cysteine ...
.


Occurrence

Diallyl disulfide and trisulfide are produced by decomposition of
allicin Allicin is an organosulfur compound obtained from garlic, a species in the family Alliaceae. It was first isolated and studied in the laboratory by Chester J. Cavallito and John Hays Bailey in 1944. When fresh garlic is chopped or crushed, the ...
, which is released upon breaking the cells of the
Alliaceae Allioideae is a subfamily of monocot flowering plants in the family Amaryllidaceae, order Asparagales. It was formerly treated as a separate family, Alliaceae. The subfamily name is derived from the generic name of the type genus, ''Allium''. ...
plants, especially
garlic Garlic (''Allium sativum'') is a species of bulbous flowering plant in the genus ''Allium''. Its close relatives include the onion, shallot, leek, chive, Allium fistulosum, Welsh onion and Allium chinense, Chinese onion. It is native to South A ...
. The diallyl disulfide yield is the highest for the
steam distillation Steam distillation is a separation process that consists in distilling water together with other volatile and non-volatile components. The steam from the boiling water carries the vapor of the volatiles to a condenser; both are cooled and ret ...
of garlic bulbs which contain about 2 wt.% of diallyl disulfide-rich oil. Diallyl disulfide can also be extracted from garlic leaves, but their oil content is significantly lower at 0.06 wt.%.


Extraction and representation

On an industrial scale, diallyl disulfide is produced from sodium disulfide and
allyl bromide Allyl bromide (3-bromopropene) is an organic halide. It is an alkylating agent used in synthesis of polymers, pharmaceuticals, synthetic perfumes and other organic compounds. Physically, allyl bromide is a colorless liquid with an irritating and p ...
or
allyl chloride Allyl chloride is the organic compound with the formula C H2=CHCH2 Cl. This colorless liquid is insoluble in water but soluble in common organic solvents. It is mainly converted to epichlorohydrin, used in the production of plastics. It is a ch ...
at temperatures of 40–60 °C in an
inert gas An inert gas is a gas that does not readily undergo chemical reactions with other chemical substances and therefore does not readily form chemical compounds. The noble gases often do not react with many substances and were historically referred to ...
atmosphere; sodium disulfide is generated ''in situ'' by reacting
sodium sulfide Sodium sulfide is a chemical compound with the formula Na2 S, or more commonly its hydrate Na2S·9 H2O. Both the anhydrous and the hydrated salts in pure crystalline form are colorless solids, although technical grades of sodium sulfide are gener ...
with
sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
. The reaction is
exothermic In thermodynamics, an exothermic process () is a thermodynamic process or reaction that releases energy from the system to its surroundings, usually in the form of heat, but also in a form of light (e.g. a spark, flame, or flash), electricity (e ...
and its theoretical efficiency of 88% has been achieved in practice. : Smaller quantities can be synthesized from the same starting materials, but in air and using
tetrabutylammonium bromide Tetrabutylammonium bromide (TBAB) is a quaternary ammonium salt with a bromide commonly used as a phase transfer catalyst. It is used to prepare many other tetrabutylammonium salts by salt metathesis reactions. The anhydrous form is a white soli ...
as a catalyst. The corresponding yield is below 82%. The major problem, both in the industrial synthesis and in the extraction from plants, is separation of diallyl disulfide from higher sulfides (diallyl trisulfide (
DATS Diallyl trisulfide (DATS), also known as Allitridin, is an organosulfur compound with the formula S(SCH2CH=CH2)2. It is one of several produced by the hydrolysis of allicin, including diallyl disulfide and diallyl tetrasulfide, DATS is one of the ...
), etc.). They have very similar physical properties and therefore, a typical commercial product contains only 80% of diallyl disulfide. The conversion of allicin to diallyl disulfide and trisulfide takes place particularly rapidly above 37 °C.


Properties


Physical characteristics

Diallyl disulfide has a strong garlic smell. It is a clear, yellowish liquid which boils at 138–139 °C (for the typical 80% purity) and has its
flash point The flash point of a material is the "lowest liquid temperature at which, under certain standardized conditions, a liquid gives off vapours in a quantity such as to be capable of forming an ignitable vapour/air mixture". (EN 60079-10-1) The fl ...
at 50 °C, a
density Density (volumetric mass density or specific mass) is the substance's mass per unit of volume. The symbol most often used for density is ''ρ'' (the lower case Greek letter rho), although the Latin letter ''D'' can also be used. Mathematical ...
of about 1.0 g/mL and a
vapor pressure Vapor pressure (or vapour pressure in English-speaking countries other than the US; see spelling differences) or equilibrium vapor pressure is defined as the pressure exerted by a vapor in thermodynamic equilibrium with its condensed phases ...
of 1 mmHg at 20 °C. It is non-polar; therefore, diallyl disulfide is insoluble in water and is soluble in fats, oils,
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
s, and non-polar solvents such as
hexane Hexane () is an organic compound, a straight-chain alkane with six carbon atoms and has the molecular formula C6H14. It is a colorless liquid, odorless when pure, and with boiling points approximately . It is widely used as a cheap, relatively ...
or
toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon. It is a colorless, water-insoluble liquid with the smell associated with paint thinners. It is a mono-substituted benzene derivative, consisting of a methyl group (CH3) at ...
.


Chemical reactions

Diallyl disulfide can be readily oxidized to
allicin Allicin is an organosulfur compound obtained from garlic, a species in the family Alliaceae. It was first isolated and studied in the laboratory by Chester J. Cavallito and John Hays Bailey in 1944. When fresh garlic is chopped or crushed, the ...
with
hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3% ...
or
peracetic acid Peracetic acid (also known as peroxyacetic acid, or PAA) is an organic compound with the formula CH3CO3H. This peroxy acid is a colorless liquid with a characteristic acrid odor reminiscent of acetic acid. It can be highly corrosive. Peracetic a ...
.
Allicin Allicin is an organosulfur compound obtained from garlic, a species in the family Alliaceae. It was first isolated and studied in the laboratory by Chester J. Cavallito and John Hays Bailey in 1944. When fresh garlic is chopped or crushed, the ...
in turn can hydrolyze giving diallyl disulfide and trisulfide. Reaction of diallyl disulfide with liquid
sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
gives a mixture containing diallyl
polysulfide Polysulfides are a class of chemical compounds containing chains of sulfur atoms. There are two main classes of polysulfides: inorganic and organic. Among the inorganic polysulfides, there are ones which contain anions, which have the general formu ...
s with as many as 22
sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
atoms in a continuous chain identified. When diallyl disulfide is heated it decomposes giving a complex mixture. The carbon-sulfur bond of diallyl disulfide is 16 kcal mol−1 weaker than the sulfur-sulfur bond (46 kcal mol−1 versus 62 kcal mol−1, respectively), with the consequence that on heating diallyl disulfide gives the allyldithio radical (AllSS•), which through addition to the double bonds in diallyl disulfide followed by fragmentation and subsequent reactions generates numerous organosulfur compounds, many of which are found in trace amounts in distilled garlic oil. In the presence of a catalyst, diallyl disulfide can combine with
alkyl halide The haloalkanes (also known as halogenoalkanes or alkyl halides) are alkanes containing one or more halogen substituents. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalkanes are widely ...
s forming 1-alkylthio-3-allylthio-1-propene and 1,3-di(alkylthio)propene.


Applications

In the presence of
iron chloride Iron chloride may refer to: * Iron(II) chloride Iron(II) chloride, also known as ferrous chloride, is the chemical compound of formula FeCl2. It is a paramagnetic solid with a high melting point. The compound is white, but typical samples are o ...
or copper chloride catalyst, or of liquid
sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
at 120 °C Diallyl disulfide can be used as a precursor for the synthesis of higher diallyl
polysulfides Polysulfides are a class of chemical compounds containing chains of sulfur atoms. There are two main classes of polysulfides: inorganic and organic. Among the inorganic polysulfides, there are ones which contain anions, which have the general form ...
(polysulfanes). In agriculture, diallyl disulfide and related diallyl polysulfides show useful activity as environmentally-benign
nematicide A nematicide is a type of chemical pesticide used to kill plant-parasitic nematodes. Nematicides have tended to be broad-spectrum toxicants possessing high volatility or other properties promoting migration through the soil. Aldicarb (Temik), a car ...
s. Diallyl disulfide is also a starting material for the synthesis of
allicin Allicin is an organosulfur compound obtained from garlic, a species in the family Alliaceae. It was first isolated and studied in the laboratory by Chester J. Cavallito and John Hays Bailey in 1944. When fresh garlic is chopped or crushed, the ...
. In the food industry, diallyl disulfide is used to improve the taste of meat, vegetables and fruits.


Biological importance


Smell and taste

The unpleasant smell of diallyl disulfide is perceived through the
transient receptor potential cation channel, member A1 Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the ''TRPA1'' (and in mice and rats by the ''Trpa1' ...
(TRPA1). This
ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
had long been present not only in humans and animals, but even in fungi. Thus,
Alliaceae Allioideae is a subfamily of monocot flowering plants in the family Amaryllidaceae, order Asparagales. It was formerly treated as a separate family, Alliaceae. The subfamily name is derived from the generic name of the type genus, ''Allium''. ...
plants have likely developed the diallyl disulfide-TRPA1 protection mechanism against predators at the early stages of the evolution.


Poisoning and detoxification

Diallyl disulfide is an efficient agent for detoxication of the cells. It significantly increases the production of the enzyme
glutathione S-transferase Glutathione ''S''-transferases (GSTs), previously known as ligandins, are a family of eukaryotic and prokaryotic phase II metabolic isozymes best known for their ability to catalyze the conjugation of the reduced form of glutathione (GSH) to x ...
(GST), which binds
electrophilic In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carri ...
toxins in the cell. Garlic therefore supports, for example, the detoxification function of liver cells ''in vitro'' and protects nerve cells from oxidative stress, also ''in vitro''. The detoxification effect may prevent symptoms of inflammation. This was confirmed in a study on rats where prolonged administration of diallyl disulfide protected poisoning of their intestinal cells. This study also showed that certain side effects of high doses of garlic oil are not attributable to the diallyl disulfide. By supporting the detoxification activity in the liver, diallyl disulfide might offer liver protection during the
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
, e.g. against
cyanide Cyanide is a naturally occurring, rapidly acting, toxic chemical that can exist in many different forms. In chemistry, a cyanide () is a chemical compound that contains a functional group. This group, known as the cyano group, consists of ...
detoxification.


Antimicrobial effect

The release of
organosulfur compound Organosulfur compounds are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.g., saccharin. Nature abounds with organosulfur compounds—sulfu ...
s upon destruction of Alliaceae plant cells has great importance, because of the antimicrobial,
insecticidal Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed to b ...
and
larvicidal A larvicide (alternatively larvacide) is an insecticide that is specifically targeted against the larval life stage of an insect. Their most common use is against mosquitoes. Larvicides may be contact poisons, stomach poisons, growth regulators, o ...
properties of those compounds. In particular, diallyl disulfide is the main reason for inhibiting the growth of
mold A mold () or mould () is one of the structures certain fungus, fungi can form. The dust-like, colored appearance of molds is due to the formation of Spore#Fungi, spores containing Secondary metabolite#Fungal secondary metabolites, fungal seco ...
s and bacteria by garlic oil. It is also acts against the
stomach ulcer The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach is ...
germ ''
Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is though ...
'', however not as efficiently as allicin. Because of its antimicrobial effects, diallyl disulfide, together with
tobramycin Tobramycin is an aminoglycoside antibiotic derived from '' Streptomyces tenebrarius'' that is used to treat various types of bacterial infections, particularly Gram-negative infections. It is especially effective against species of ''Pseudomonas ...
, is included in preparations which are used for selective decontamination of the organs (e.g. gut) before surgical operations. A clinical study showed that such preparations prevent
endotoxemia Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...
in heart valve operations.


Protection against colon cancer

Garlic can prevent
colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...
, and several studies revealed that diallyl disulfide is a major component responsible for this action. The effect is dose dependent as demonstrated on mice. Diallyl disulfide affects cancer cells much more strongly than normal cells. It also results in a strong and dose-dependent accumulation of several agents, such as reactive oxygen species, which activate enzyme and lead to destruction of cancer cells.


Protection against cardiovascular disease

There is evidence that garlic may prevent the development of cardiovascular diseases. A possible reason for some of these diseases, such as
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...
or
coronary heart disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...
is
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...
. The latter is reduced by diallyl disulfide by assisting in the detoxification of the cell, as well as some other mechanisms. By activating the TRPA1 ion channel, diallyl disulfide leads to a short-term lowering of blood pressure.


Safety

Diallyl disulfide is a skin irritant and an
allergen An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called allergies. In technical terms ...
. In particular, it is the main cause of garlic allergy (
allergic contact dermatitis Allergic contact dermatitis (ACD) is a form of contact dermatitis that is the manifestation of an allergic response caused by contact with a substance; the other type being irritant contact dermatitis (ICD). Although less common than ICD, ACD is ...
to garlic). The allergy usually starts at the fingertips and cannot be prevented by wearing gloves because diallyl disulfide penetrates through most commercial glove types. The median
lethal dose In toxicology, the lethal dose (LD) is an indication of the lethal toxicity of a given substance or type of radiation. Because resistance varies from one individual to another, the "lethal dose" represents a dose (usually recorded as dose per kilog ...
(LD50) for oral intake in
rat Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include ''Neotoma'' ( pack rats), ''Bandicota'' (bandicoot ...
s is 260 mg per kg of body weight and it is 3.6 g/kg for dermal intake. High doses of 5 g/kg placed on the skin of cats cause death through
hemolytic anemia Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...
. Diallyl disulfide can be easily detected in the air or in the blood with
gas chromatography Gas chromatography (GC) is a common type of chromatography used in analytical chemistry for separating and analyzing compounds that can be vaporized without decomposition. Typical uses of GC include testing the purity of a particular substance, ...
.


See also

* Allyl propyl disulfide


References

{{Transient receptor potential channel modulators Organic disulfides Allyl compounds Nematicides Histone deacetylase inhibitors